Which chemicals are associated with a peripheral neuropathy that is thought at least partly to be caused by their symmetrical structures allowing parts of the neurons to be cross-linked but is definitely associated with axonal swelling.
A. Carbon dioxide and nitrogen gas
B. Carbon disulfide and n-hexane
C. Hydrogen cyanide and hydrogen sulfide gas
D. Lead and mercury
Answer: B. Note. As the name n-hexane suggest n-hexane is six carbons long. Everything else are much simpler compounds or in the case of nitrogen, lead and mercury, elements.
Which of the following is both an antidote used to treat multiple classes of neurotoxicants (e.g., drug, pesticide, plant-based) as well as something that can cause neurotransmitter associated toxicity itself from being overexposed to its effects as either a drug or a plant-based toxicant?
A. Atropine
B. Bismuth
C. Cyanide
D. Digoxin
Answer: A. Notes [need to consolidate] Bismuth is an element and not a compound made inside plants. Cyanide is a toxicant but not an antidote and it acts through the mitochondria and not the nerves. Digoxin is a plant-based drug and toxicant, but it has a narrow therapeutic index and is not an antidote. Plus, it is a cardiac glycoside with more activity in the heart than brain and it acts by inhibiting sodium/potassium ATPase pumps so acting via ions involved in the polarization of nerves and the transport of neurotransmitters but are not neurotransmitters themselves. In contrast, cholinergic and anticholinergic compounds either act like, act on, or in the case of atropine, antagonistically compete with the neurotransmitter acetylcholine. Atropine is used to treat cholinergic toxicity from cholinesterase inhibiting insecticides (i.e., organophosphate, carbamate) but also can work against plant-based toxicants (e.g., physostigmine from Calabar bean). Atropine competes with binding at the muscarinic acetylcholine receptors. However, when too much is given as a drug and/or consumed (e.g., jimsonweed), it can cause anticholinergic toxicity. Bismuth is a metal. Cyanide, while it can be found in cyanogenic plants (e.g., cassava, bitter almonds) is not used as an approved drug. Digoxin is a cardiac glycoside. While it is found in plants (e.g., foxglove) and is used pharmacologically, it acts on cardiac channels and is not primarily a neurotoxicant nor does its mode of action work through neurotransmitters. Plus, it has a narrow therapeutic range, something not desirable in an antidote.
In addition to in vivo animal rodent models in vitro and other alternative approaches to developmental neurotoxicology have been developed. A startle response in young mice or rats is most likely to be recapitulated using what model?
A. Epigenetic approach
B. Human neural progenitor cells
C. Neural cells plated on microelectrode arrays
D. Zebrafish embryos
Answer: D Notes: Neural cells plated on microelectrode arrays can identify chemicals which increase (e.g., nicotine, lindane, RDX) firing rates by interacting with different receptors (e.g., nicotinic, GABA). However, without being connected to cells taking in outside stimuli (e.g., light, movement, sound) they cannot be "startled." Zebrafish embryos, like the adult fish, having begun developing sensory organs and their respective inputs, can be startled.
Moonshine production can cause neurotoxicity and blindness when distillation is done improperly, and the ethanol gets mixed with lighter and more toxic solvents (e.g., methanol). However, there can be other health risks and neurotoxicity associated with using improper distillation equipment (e.g., car radiators). A patient comes in complaining of stomach and joint pains, headaches and memory issues. During the assessment they admit to making their own moonshine using a homemade still that involved repurposing a car radiator as a condenser. What is the most likely cause of these symptoms?
A. Aluminum leaching out of the radiator
B. Antifreeze (i.e., ethylene glycol) leftover in the radiator
C. Copper leaching out of the radiator
D. Lead leaching out of the radiator
Answer: D. Aluminum taken orally tends to have very poor bioavailability. Intravenous exposure (e.g., dialysate, parenteral nutrition) would change the risk. And although ethanol solutions have been given intravenously, that tends to be in hospital settings and not recreationally. Ethylene glycol damages the kidneys. Copper can cause toxicity, but there tends to be genetic susceptibility towards its accumulation. Joint pain and memory loss (in adults) tends to be more indicative of lead poisoning.
The blood brain barrier while not an absolute barrier prevents many potential neurotoxicants from entering the brain and neurons. Some compounds like MPTP readily cross this barrier while others, like its Parkinson symptom causing metabolite MPP+ is kept out due to their properties (e.g., charge). But if formed inside the brain MPP+ can damage dopaminergic neurons and is taken up into them by the dopamine uptake system. What is a similar situation where a toxicant can cross a barrier to damage the nervous system by taking advantage of an existing transport system designed to bring in endogenous molecules.
A. Alcohol's (i.e., ethanol) small size and lipophilic nature allow it to cross and disrupt cell membranes.
B. Antidiarrheal drug loperamide is a p-glycoprotein substrate
C. Antineoplastic drug vincristine binds to tubulin and causes microtubule depolymerization
D. Axonal transport of tetanus toxin allows it to travel across long peripheral nerves
Answer: D. Note: Ethanol bypasses transport systems. P-glycoprotein is an efflux transported. Being its substrate makes crossing certain barriers into areas protected with this transporter (e.g., gut, brain) less likely. Rather than using a transport system, vincristine destroys one. Tetanus toxin is able to move from a dirty cut on a toe or finger all the way up the peripheral nerve and as reflexive movements away from painful stimulus to the hand or foot can demonstrate these nerves lead directly to the spinal cord providing a central nervous system entry for tetanus toxic.
